During the insulin-mediated adipocyte conversion of confluent 3T3-L1 cells, glutamine synthetase (GS) specific activity increases more than 100-fold. Incubation of the adipocytes for 24 h with dibutyryl cAMP (Bt2cAMP) plus theophylline decreases GS specific activity by greater then 70 percent. Incubation of 3T3 adiopocytes with hydrocortisone increases GS activity by 1.5-to 2-fold. Immunotitration of GS activity from 3T3 adipocytes indicates that observed changes are due to changes in the cellular content of GS molecules. The Bt2cAMP-mediated decrease in glutamine synthetase activity results from a decrease in the synthesis rate and an increase in the degradation rate of the enzyme. Our current effects are directed toward determining the effects of insulin, glucocorticoids and other effectors on the rate of GS synthesis and degradation. In addition, we will attempt to determine whether GS in 3T3-L1 adipocytes might be subject to regulation by covalent modification.